Detection of RBM15-MKL1 Fusion Was Useful for Diagnosis and Monitoring of Minimal Residual Disease in Infant Acute Megakaryoblastic Leukemia

Acute megakaryocytic leukemia (AMKL) with t(1;22)(p13;q13) is a distinct category of myeloid leukemia by WHO classification and mainly reported in infants and young children. Accurate diagnosis of this type of AMKL can be difficult, because a subset of patients have a bone marrow (BM) blast percentage of less than 20% due to BM fibrosis. Therefore, it is possible that past studies have underestimated this type of AMKL. We present here the case of a 4-month-old female AMKL patient who was diagnosed by presence of the RBM15-MKL1 (OTT-MAL) fusion transcript by RT-PCR. In addition, we monitored RBM15-MKL1 fusion at several time points as a marker of minimal residual disease (MRD), and found that it was continuously negative after the first induction chemotherapy even by nested RT-PCR. Detection of the RBM15-MKL1 fusion transcript thus seems to be useful for accurate diagnosis of AMKL with t(1;22)(p13;q13). We recommend that the RBM15-MKL1 fusion transcript be analyzed for all suspected AMKL in infants and young children. Furthermore, monitoring of MRD using this fusion transcript would be useful in treatment of AMKL with t(1;22)(p13;q13)

Clonal expansion of Epstein-Barr virus (EBV)-infected γδ T cells in patients with chronic active EBV disease and hydroa vacciniforme-like eruptions

Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is a systemic EBV-positive lymphoproliferative disorder characterized by fever, lymphadenopathy, and splenomegaly. Patients with CAEBV may present with cutaneous symptoms, including hypersensitivity to mosquito bites and hydroa vacciniforme (HV)-like eruptions. HV is a rare photodermatosis characterized by vesicles and crust formation after exposure to sunlight, with onset in childhood, and is associated with latent EBV infection. While γδ T cells have recently been demonstrated to be the major EBV-infected cell population in HV, the immunophenotypic features of EBV-infected γδ T cells in CAEBV with HV-like eruptions or HV remain largely undetermined. We describe three patients with CAEBV whose γδ T cells were found to be the major cellular target of EBV. HV-like eruptions were observed in two of these patients. A clonally expanded subpopulation of γδ T cells that were highly activated and T cell receptor Vγ9- and Vδ2-positive cells was demonstrated in all patients. We also show that the clonally expanded γδ T cells infiltrated into the HV-like eruptions in one patient from whom skin biopsy specimens were available. These results suggest the pathogenic roles of clonally expanded γδ T cells infected by EBV in patients with CAEBV and HV-like eruptions. © 2012 The Japanese Society of Hematology

Flow cytometric analysis of skin blister fluid induced by mosquito bites in a patient with chronic active Epstein-Barr virus infection

金沢大学医薬保健研究域医学系In chronic active Epstein-Barr virus (EBV) infection (CAEBV), ectopic EBV infection has been described in T or natural killer (NK) cells. NK cell-type infection (NK-CAEBV) is characterized by large granular lymphocytosis, high IgE levels and unusual reactions to mosquito bites, including severe local skin reactions, fever and liver dysfunction. However, the mechanisms underlying these reactions remain undetermined. Herein, we describe a patient with NK-CAEBV whose blister fluid after mosquito bites was analyzed. The patient exhibited significant increases in the percentage of CD56+ NK cells in the fluid compared with a simple mosquito allergy, in which the majority of infiltrated cells were CD203c+ cells, indicating basophils and/or mast cells. His fluid also contained CD203c+ cells, and his circulating basophils were activated by mosquito extracts in vitro. These results suggest that CD203c+ cells as well as NK cells may play pathogenic roles in the severe skin reactions to mosquito bites in NK-CAEBV. © 2009 The Japanese Society of Hematology.出版者に照会中.2010年12月より全文公開予定

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Electrocardiographic Changes before and after Surgical Correction of Isolated pulmonic Stenosis

Electrocardiographic, vectorcardiographic and phonocardiographic changes were studied before and after surgical correction of isolated pulmonic stenosis. 1. Before operation, the maximal right ventricular systolic pressure were correlated well with the T wave changes, such as mean electrie T axis, direction of maximal T vector in each plane, spatial maximal QRS-T angle, ratio of spatial magnitude of T to QRS vector, and the QRS wave changes, such as height of Rv(1), sum of Rv(1) and Sv(5), direction of maximal QRS vector in frontal plane, rotation of QRS loop in horizontal plane, configuration of QRSv(1). After operation, in addition to those above, R/Sv(1), Rv(1)+Sv(5)/Sv(1)+Rv(5) and mean electric QRS axis tended to improve much more within the first one year after operation than thereafter. 2. The appearance of RBBB type were found more frequent after operation than before, and thought to be due to the decreasing right ventricular systolic overloading, or its combination with operative invasion to peripheral network of right bundle branch. 3. The more or less abnormal findings were revealed in twenty one cases, the remaining one was appreciated to be normal one hundred and twenty five months after operation

Absence of the Sternocleidomastoid Muscle in a Patient That Underwent Neck Dissection for Squamous Cell Carcinoma of the Tongue

The congenital absence of a skeletal muscle is a rare cause of congenital muscular torticollis, and the condition is associated with various unusual anatomical structures. We describe a rare case of congenital absence of the sternocleidomastoid muscle associated with squamous cell carcinoma of the tongue in a patient who underwent neck dissection. In this case, both the external jugular vein and the spinal accessory nerve were absent. However, we found that branches of the C3 nerve extended from the cervical plexus to the trapezius muscle and seemed to be acting as trapezius muscle motor nerves in place of the accessory nerve. After the operation, the patient was able to lift and abduct his right arm, and his shoulder did not droop